Respiratory diseases encompass pathological conditions affecting the organs and tissues that make gas exchange possible in higher organisms. One such type of respiratory disease is asthma. Asthma is a common disease causing lost productivity and quality of life and consuming large amounts of health care costs. Mild to moderate asthma is usually well-controlled with inhaled glucocorticoids (ICS) in combination with long-acting β2-adrenoceptor agonists (LABA), so-called combination therapy. However, in patients with severe disease there are episodes of loss of asthma control. The majority of exacerbations of asthma (and of COPD) are due to viral infection of the lower respiratory tract, with rhinovirus (RV), respiratory syncytial virus (RSV) and influenza virus (InfV) being most commonly detected. The occurrence of exacerbations in patients who are taking combination therapy defines the exacerbations as resistant to treatment with glucocorticoids. This resistance can be viewed as an insensitivity of the viral inflammation to treatment by ICS/LABA, or more specifically that acute viral infection turns off some of the beneficial effects of glucocorticoid (GC). This acute GC-resistant exacerbation may be viewed as additional to an underlying state of the structural and inflammatory cells of the airways. In patients with severe obstructive disease, lung function does not normalize, even in the absence of respiratory tract infection and with compliance when treated with ICS/LABA. Thus, there is also a GC resistance in these chronic respiratory diseases that is not necessarily related to viral infection.
The prevalence of severe steroid resistant asthma is estimated to comprise 5% of all asthmatics. Given the high prevalence of asthma (˜10%), there are approximately 125,000 Australians who are unable to achieve normal lung function when fully compliant with best-practice therapy, or who need oral steroids to maintain control. These patients are at increased risk of more severe exacerbations/death from asthma, have lower quality of life, higher frequency of hospital admissions and impact on the health care resources. Some patients with moderate and severe asthma, especially those who smoke, have unexpectedly limited responses to ICS.
There is a need for new and/or improved treatments or preventatives for respiratory diseases, particularly in patients who have experienced, or who are experiencing, resistance to treatment with a glucocorticoid.
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